Intraoperative alteration in the vital signs of diabetic patients during cataract surgery with local anesthesia.

PURPOSE: Diabetic patients often have systemic circulation diseases which may cause serious systemic complications during ophthalmic surgeries with local anesthesia. The purpose of this study is to evaluate the intraoperative alteration of the vital signs in diabetic patients during cataract surgery with local anesthesia.
METHODS: Clinical records of 428 patients who underwent cataract surgeries with local anesthesia were reviewed. The parameters measured were systolic/diastolic blood pressures and pulse rates at pre-operation, 5, 10 and 15 minutes during the surgeries. The factors were compared between non-diabetic patients (n = 325) and diabetic patients (n = 103).
RESULTS: Diabetic patients had significantly higher fasting blood sugar and preoperative pulse rate. Diabetic patients showed significantly higher systolic blood pressure compared to non-diabetic patients at 5 and 10 minutes from the beginning of surgery (p = 0.0093 and 0.0075, respectively). In the non-diabetic patients, the pulse rate was significantly decreased at 5 minutes from the beginning of surgery (p = 4.74 x 10-8) which was maintained during the surgery, but no change was observed in the pulse rate of the diabetic patients.
CONCLUSIONS: Diabetic patients showed higher systolic blood pressure and pulse rate during cataract surgeries with local anesthesia, which should be monitored carefully by the physicians to avoid possible systemic complications.

Introduction

Diabetes mellitus (DM) is a prevalent disorder in the developed countries which causes several complications in the systemic circulation including hypertension, cardiac infarction and strokes [1]. Cardiovascular autonomic neuropathy is frequently observed in patients with DM. As anesthesia has a marked effect on peri-operative autonomic function, the interplay between diabetic neuropathy and anesthesia may result in unexpected hemodynamic instability during surgery [2]. Those complications may occur during ophthalmic surgeries performed under local anesthesia, which may cause serious problems in the ocular and systemic conditions [3]. To investigate the risk factors of intraoperative abnormal vital signs when performing cataract surgeries with local anesthesia is an important issue for ophthalmologists. On the other hand, a recent technical advancement of cataract surgery enables safer and faster operation which expands the indication of cataract surgery with local anesthesia to the patients with more systemic risk factors [4, 5]. However, few studies have been reported regarding the hemodynamic state of DM patients during a recent minimal invasive cataract surgery with local anesthesia [6].

Here, we conducted a statistical evaluation on the intraoperative alteration of the vital signs of DM patients during cataract surgery with local anesthesia.

Materials and methods

This study is a retrospective chart review approved by the Institutional Review Board at the Osaka City University Graduate School of Medicine (No. 2020–153) and was conducted in accordance with the Declaration of Helsinki. All cases in this study were Japanese individuals recruited from the Department of Ophthalmology at Osaka City University Hospital in Japan. Written informed consent for using ordinary clinical data in following retrospective studies were obtained from all subjects at their first visit to the hospital and an opt-out for this study was indicated at the hospital website.

Clinical records of 428 patients who underwent the initial cataract surgeries with local anesthesia between June 1st 2018 and May 31th 2019 were reviewed after anonymization of personal information.

The standard procedure of cataract surgery in the present study was as follows: 1) All patients were advised to take all their usual medications with a small amount of water on the morning of surgery. 2) Abstinence from solid food 2 hours preoperatively. 3) Pupil dilation with 10% phenylephrine and 1% tropicamide eyedrops. 4) Topical anesthesia with 0.4% oxybuprocaine was administered twice preoperatively with 5-minute intervals between instillations. 5) A certified nurse inserted a 22-gauge caliber after a venous puncture in the arm in either upper extremity, depending on vein availability. 6) The parameters monitored intraoperatively included continuous pulse rate, pulse oximetry, electrocardiography, and blood pressure every 5 minutes recorded. 7) Several topical drops of 4% lidocaine hydrochloride and a sub-Tenon’s block with 0.5–1.0 ml of 2% lidocaine hydrochloride were applied to the operated eye. 8) A 2.4 mm self-sealing sclerocorneal incision was made and phacoemulsification + aspiration was performed. 9) A foldable posterior chamber intraocular lens was implanted. In the present study, all cataract surgeries were performed by experienced surgeons. Cases with any complications, such as early perforation, capsule rupture or zonular disinsertion were excluded from the study. The surgeries required operation time for more than 50 minutes were also excluded.

Baseline parameters of the patients collected were age, gender, body weight, body mass index (BMI), fasting blood sugar (FBS) at the latest visit, estimated glomerular filtration rate (eGFR), medications for DM or systemic hypertension. In the present study, the patients receiving any medication for DM were determined as diabetic patients. Ones receiving only diet therapy were not determined as diabetic patients. The parameters measured were systolic/diastolic blood pressures (SBP/DBP) and pulse rates (PR) at pre-operation, 5, 10 and 15 minutes during the surgeries. The factors were compared between non-diabetic patients (n = 325) and diabetic patients (n = 103).

For statistical analysis, each clinical factor was evaluated by paired or unpaired t-test where applicable between any two groups. To find the independent factors associated with the vital signs during the surgery multiple regression analyses were performed with explanatory variables including age, gender, BMI, FBS, eGFR, pre-operative SBP/DBP and PR, the presence or absence of DM and the presence or absence of hypertension medication.

We used EZR1.27 software for all the statistical analyses [7]. P values of 0.05 or less were considered to be statistically significant.

Results

Clinical characteristics of the patients with or without DM are summarized in Table 1. The patients with DM showed significantly higher BMI, higher FBS, higher pre-operative pulse rate and higher proportion of patients receiving hypertension medication compared to the patients without DM.

Table 1

Clinical characteristics of the patients with or without DM.

	DM- (n = 325)	DM+ (n = 103)	P-value
Gender	143/182	49/54	0.60 *
(male/female)
Age	75.3±10.4	73.1±9.4	0.057 †
(mean±SD)
BMI	23.2±3.7	24.1±3.9	0.047
FBS (mg/dl)	103.2±18.0	148.6±71.3	4.62×10−23 †
(mean±SD)
eGFR (mL/min/1.73m2)	61.3±17.7	58.0±21.2	0.12
(mean±SD)
Pre-operative SBP (mmHg) (mean±SD)	128.1±19.9	131.5±19.0	0.12 †
Pre-operative DSBP (mmHg) (mean±SD)	70.7±13.2	68.7±11.4	0.16 †
Pre-operative PR (beats/min) (mean±SD)	69.5±11.8	72.7±12.0	0.017 †
Hypertension Medication (yes/no) (%)	197/128 (60.6)	79/24 (76.7)	0.0043 *
Operation time	21.5±8.8	22.4±9.8	0.35
(minutes) (mean±SD)

DM; diabetes mellitus, BMI; body mass index, FBS; fasting blood sugar, eGFR; estimated glomerular filtration rate, SBP; systolic blood pressure, DSBP; diastolic blood pressure, PR; pulse rate.

* χ2 test

† unpaired t-test. Values are indicated as mean ± standard deviation where applicable.

The mean SBPs of DM and non-DM patients significantly increased at 5 minutes (9.50×10−15 and 3.23×10−49, respectively) and gradually decreased over time. The mean SBPs of DM patients was significantly higher than those of non-DM patients at 5 and 10 minutes from the beginning of surgery (Fig 1). The mean DBPs in DM and non-DM groups significantly increased at 5 minutes (9.64×10−16 and 5.27×10−39, respectively), which sustained up to 15 minutes from the beginning of surgery (Fig 2). There was no difference in the mean DBPs between two groups at any period measured. The mean PRs of DM patients was significantly higher than those of non-DM patients at all time point measured (Fig 3). A significant decrease in the mean PR was observed at 5 minutes from the beginning of surgery in non-DM patients, but not in DM patients.

Fig 1

Time course of systolic blood pressure in the DM group (solid line) and non-DM group (dashed line).

P-values are the results of unpaired t-test.

Fig 2

Time course of diastolic blood pressure in the DM group (solid line) and non-DM group (dashed line).

P-values are the results of unpaired t-test.

Fig 3

Time course of pulse rate in the DM group (solid line) and non-DM group (dashed line).

P-values are the results of unpaired or paired (*) t-test.

The multiple regression analyses demonstrated that the significant association factors for SBP were FBS and eGFR at 5 and 10 minutes from the beginning of surgery (Table 2), and the significant association factor for PR was the presence of DM at 5, 10 and 15 minutes from the beginning of surgery (Table 3). FBS was also associated with the PR at 5 minutes.

Table 2

Results of stepwise multiple regression analysis for a systolic blood pressure.

Explanatory variables including age, gender, BMI, FBS, eGFR, pre-operative SBP/DBP and PR, the presence or absence of DM and the presence or absence of hypertension medication.

A. Significant association factors at 5 minutes.
	Estimate	SE	t value	P value
FBS	0.12	0.024	5.05	6.70×10−7
eGFR	-0.20	0.055	-3.59	3.64×10−4
B. Significant association factors at 10 minutes.
	Estimate	SE	t value	P value
FBS	0.085	0.024	3.61	3.38×10−4
eGFR	-0.20	0.054	-3.74	2.10×10−4

DM; diabetes mellitus, BMI; body mass index, FBS; fasting blood sugar, eGFR; estimated glomerular filtration rate, SBP; systolic blood pressure, DSBP; diastolic blood pressure, PR; pulse rate, SE; standard error.

Table 3

Results of stepwise multiple regression analysis for a pulse rate.

Explanatory variables including age, gender, BMI, FBS, eGFR, pre-operative SBP/DBP and PR, the presence or absence of DM and the presence or absence of hypertension medication.

A. Significant association factors at 5 minutes.
	Estimate	SE	t value	P value
FBS	0.032	0.014	2.19	2.93×10−2
DM+	4.63	1.44	3.21	1.41×10−3
B. Significant association factors at 10 minutes.
	Estimate	SE	t value	P value
DM+	5.85	1.26	4.65	4.36×10−6
C. Significant association factors at 15 minutes.
	Estimate	SE	t value	P value
DM+	5.95	1.21	4.91	1.28×10−6

DM; diabetes mellitus, BMI; body mass index, FBS; fasting blood sugar, eGFR; estimated glomerular filtration rate, SBP; systolic blood pressure, DSBP; diastolic blood pressure, PR; pulse rate, SE; standard error, DM+; presence of diabetes mellitus.

Discussion

We evaluated the intraoperative alteration of vital signs in DM patients during cataract surgery with local anesthesia and demonstrated that DM patients showed significantly higher SBP and PR than non-DM patients during cataract surgery with local anesthesia.

In the present day, cataract surgery is established with a fast and low invasive procedure which enables many diabetic patients to undergo cataract surgeries without serious ocular and systemic complications [4, 5]. However, an anxiety for the surgery may still affect some physical or mental conditions of the patients during the operation with local anesthesia [3, 8], hence we must pay attention to any changes in the vital signs of the patients during the surgery. In particular, diabetic patients often exhibit systemic hypertension and following cardiovascular diseases which may cause serious prognosis, which necessitates more careful control of blood pressure and pulse rate during the surgery [9]. In the present study, the mean baseline SBP/DBP in DM group was not significantly different from that of non-DM group probably because many patients received medications for systemic hypertension, which could influence the results. However, the mean SBP in DM group was more than 150 mmHg at 5–10 minutes from the beginning of surgery, which was significantly higher than that of non-DM group. Some recent reports recommended to target SBP/DBP at 130-140/80-90 mmHg in adults with DM and arterial hypertension in order to reduce the risk of lethal events [10-12]. Hence, our results indicate the need of more careful monitoring and control of SBP during cataract surgery in DM patients. The multiple regression analyses revealed that SBP was significantly associated with FBS and eGFR which was consistent with previous reports [6, 13, 14]. Hence, the higher SBP in DM patients may reflect the abnormal renal function and glucose metabolism. In addition, the mean pulse rate in DM group was significantly higher at all time point measured in this study. Interestingly, the mean pulse rate in non-DM group was significantly decreased after 5 minutes from the beginning of surgery which was not observed in DM group. A previous report demonstrated that DM patients have an alteration of the autonomic nervous system which is clearly more marked under mental stress than in resting condition [9]. We considered that a temporal elevation of PR occurred preoperatively with an anxiety for the surgery with local anesthesia which was attenuated over time with autonomic control in non-DM patients, but this function did not work in DM patients. This hypothesis was supported with the results of multiple regression analyses which determined the presence of DM as the only significant factor associated with the perioperative PR.

The limitation of the present study is mostly related to the retrospective study design which might be affected by undefined confounding factors. For example, the PR and SBP could be affected by the pain sensation during the surgery, which was not evaluated in the present study. A hypotensive drug might be injected for the patients who showed sustained high SBP during the surgery depends on the surgeons’ discretions, which could influence the results of the present study. A systematic prospective study may warrant the results of this study. However, our results indicated that DM patients could show higher SBP and PR than non-DM patients during the latest cataract surgery. Therefore, we still need to be more careful with the vital signs of DM patients during cataract surgeries with local anesthesia.

(XLSX)

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31 Jan 2022

Intraoperative alteration in the vital signs of diabetic patients during cataract surgery with local anesthesia.

PLOS ONE

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Dear Shigeru Honda

Manuscript entitled PONE-D-21-22264 "Intraoperative alteration in the vital signs of diabetic patients during cataract surgery with local anesthesia." which you submitted to PLOS ONE, has been reviewed.

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Reviewer #1: This study evaluated the intraoperative vital signs and associated factors under local anesthesia. I propose several points to be clarified.

1. The authors described the operation was performed within 30 mins. Please provide the mean operation time in table 1.

2. Were there any patients who needed additional medications due to high blood pressure before the surgery? If so, please describe that point in method section, and provide that information in result section such as the proportion of patients who were administered additional medication to control the high BP.

3. Please provide the ocular information affecting the cataract surgery. Were all cases senile cataract? And if it is possible, axial length, presence of uveitis, or previous surgical history should be provided.

4. The pulse rate and systolic BP can be affected by the pain sensation due to surgical procedure such as iris touching. The pupil of DM patients usually dilated poorly. If it is possible, please state the information about the pupil size or posterior synechia.

5. In the same context as point 4, young patients usually feel pain better than older patients. Although, the mean age of two groups is not different significantly, DM patients were younger in table 1. I think presenting the factors which is not significant (including age) in table 2 and 3 would be helpful for better understanding of readers.

Reviewer #2: The authors evaluated the intraoperative alteration of the vital signs in diabetic patients during cataract surgery with local anesthesia and emphasized the need for careful monitoring by the physicians to avoid possible systemic complications However, there are several concerns to be clarified before publication.

1. In figure 3, I think it is necessary to correct the figure legend as "Time course of pulse rate"

2. In figure 1, the mean SBP in DM group was more than 150 mmHg at 5-10 minutes from the beginning of surgery. Did you take any treatment for that?

3. In general, cataract surgery does not cause much pain, but blood pressure and pulse rate could be different depending on the severity of pain. It is better to describe whether you have considered this.

4. There were several reports that bradycardia, hypotension associated lidocaine toxicity. Therefore, the possibility that lidocaine administration used for sub-tenon’s block may affect purse rate or blood pressure should be considered.

**********

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Reviewer #1: No

Reviewer #2: Yes: Areum Jeong

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2 Feb 2022

Author response to the reviewers

We greatly appreciate the reviewers for many valuable comments given to our manuscript. We would provide the point-by-point answers for each comment. In addition, we would announce that the number of DM group has been changed from 104 to 103 after recounting the subjects and values of associated parameters have been slightly changed after recalculation, which does not affect the conclusion.

Reviewer #1: This study evaluated the intraoperative vital signs and associated factors under local anesthesia. I propose several points to be clarified.

1. The authors described the operation was performed within 30 mins. Please provide the mean operation time in table 1.

Response: Thank you very much for this comment. Firstly, we apologize for a mistyping of operation time. Actually, all surgeries were performed within 50 minutes (not 30 minutes) which has been corrected in the text (page 6, line 9). The mean operation times have been added in Table 1. In addition, vales of BMI and eGFR have also been presented in Table 1.

2. Were there any patients who needed additional medications due to high blood pressure before the surgery? If so, please describe that point in method section, and provide that information in result section such as the proportion of patients who were administered additional medication to control the high BP.

Response: We do not use additional hypotensive drugs before cataract surgery and rarely use such drugs during the surgery. If systolic BP of a patient is over 200 mmHg we firstly advise the patient to relax and repeat BP measurements several times (usually every 5 minutes). If BP is not decreased after repeated BP measurements, an injection of hypotensive drug might be used depends on surgeon’s discretion. Hence, it is quite rare to use additional hypotensive drugs within 15 minutes from the beginning of surgeries. However, we have mentioned about the possible use of hypotensive drugs as a limitation of this study in discussion part. (page 15, line 4-6)

3. Please provide the ocular information affecting the cataract surgery. Were all cases senile cataract? And if it is possible, axial length, presence of uveitis, or previous surgical history should be provided.

Response: Thank you for this comment. We agree that ocular status may affect cataract surgery and difficult procedures might cause intraoperative pain which could influence vital signs. However, in the present study, we obtained the data after anonymization of personal information (patient’s name, ID of clinical record etc.) and no correspondence table was made. Hence, we cannot obtain additional data about ocular status or past history.

4. The pulse rate and systolic BP can be affected by the pain sensation due to surgical procedure such as iris touching. The pupil of DM patients usually dilated poorly. If it is possible, please state the information about the pupil size or posterior synechia.

Response: We really appreciate the reviewer for this advice since we did not include intraoperative pain as a possible association factor with vital signs. Unfortunately, we cannot search additional information from anonymized data. Therefore, we have mentioned the possible influence of intraoperative pain as a limitation of this study in discussion part. (page 15, line 2-4)

5. In the same context as point 4, young patients usually feel pain better than older patients. Although, the mean age of two groups is not different significantly, DM patients were younger in table 1. I think presenting the factors which is not significant (including age) in table 2 and 3 would be helpful for better understanding of readers.

Response: We have presented all explanatory variables in Table 2 and 3 which should help the readers to understand non-significant factors.

Reviewer #2: The authors evaluated the intraoperative alteration of the vital signs in diabetic patients during cataract surgery with local anesthesia and emphasized the need for careful monitoring by the physicians to avoid possible systemic complications However, there are several concerns to be clarified before publication.

1. In figure 3, I think it is necessary to correct the figure legend as "Time course of pulse rate"

Response: Thank you very much for this comment. We have corrected the mistyping.

2. In figure 1, the mean SBP in DM group was more than 150 mmHg at 5-10 minutes from the beginning of surgery. Did you take any treatment for that?

Response: We rarely use additional hypotensive drugs during cataract surgery. If systolic BP of a patient is over 200 mmHg we firstly advise the patient to relax and repeat BP measurements several times (usually every 5 minutes). If BP is not decreased after repeated BP measurements, an injection of hypotensive drug might be used depends on surgeon’s discretion. Hence, it is quite rare to use additional hypotensive drugs within 15 minutes from the beginning of surgeries. However, we have mentioned about the possible use of hypotensive drugs as a limitation of this study in discussion part. (page 15, line 4-6)

3. In general, cataract surgery does not cause much pain, but blood pressure and pulse rate could be different depending on the severity of pain. It is better to describe whether you have considered this.

Response: We appreciate the reviewer for this advice. Actually, we did not evaluate intraoperative pain in this study. However, unfortunately, we cannot perform further evaluation for additional factors since the original data of present study were obtained after anonymization of personal information (patient’s name, ID of clinical record etc.) without correspondence table. Therefore, we have mentioned the possible influence of intraoperative pain as a limitation of this study in discussion part. (page 15, line 2-4)

4. There were several reports that bradycardia, hypotension associated lidocaine toxicity. Therefore, the possibility that lidocaine administration used for sub-tenon’s block may affect purse rate or blood pressure should be considered.

Response: Thank you for this comment. We agree that lidocaine may affect vital signs. In the present study, sub-Tenon’s lidocaine was administrated for both of DM patients and non-DM patients, so we consider that the difference between these two groups would remain under the possible influence of lidocaine.

Revised parts are indicated in red. We hope that all reviewers’ comments have been adequately addressed. Again, thank you so much for reviewing our manuscript.

Submitted filename: Author response.docx

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24 Feb 2022

Intraoperative alteration in the vital signs of diabetic patients during cataract surgery with local anesthesia.

PONE-D-21-22264R1

Dear Dr. Honda,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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Reviewer #1: (No Response)

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Reviewer #1: The manuscript has been well improved. I think most of the comments have been addressed. In my opinion this paper is worth to be published in Plos one.

Reviewer #2: (No Response)

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14 Mar 2022

PONE-D-21-22264R1

Intraoperative alteration in the vital signs of diabetic patients during cataract surgery with local anesthesia.

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